AB0402 PHARMACOKINETICS AND SAFETY OF CT-P47, A PROPOSED TOCILIZUMAB BIOSIMILAR, IN COMPARISON WITH EU-APPROVED TOCILIZUMAB; A PHASE 1, RANDOMIZED, DOUBLE-BLIND, TWO-ARM, SINGLE-DOSE STUDY IN HEALTHY SUBJECTS
Authors: K. S. Yu, B. Kim, D. Shin, M. K. Park, J. G. Hwang, M. Kim, H. Chung, J. Ghim, J. Y. Chung, J. S. Smolen, G. R. Burmester, S. H. Kim, Y. Bae, D. Jeon, G. Yang, J. Yoo, J. Bae, E. Keystone
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> CT-P47 is a recombinant humanized monoclonal antibody that was developed as a proposed biosimilar of tocilizumab. <h3>Objectives</h3> The purpose of this study was to compare the pharmacokinetics (PK), safety, and immunogenicity of CT-P47 and EU-approved tocilizumab (EU-tocilizumab) up to 42 days after a single subcutaneous injection of 162 mg of each product in healthy subjects. <h3>Methods</h3> 289 healthy subjects aged 19 to 55 years were randomly assigned 1:1 to receive either CT-P47 or EU-tocilizumab. The primary PK endpoints included area under the serum concentration-time curve (AUC) from time zero to infinity (AUC<sub>0-inf</sub>), AUC from time zero to the last quantifiable concentration (AUC<sub>0-last</sub>), and maximum serum concentration (C<sub>max</sub>). Secondary endpoints were additional PK, safety, and immunogenicity. <h3>Results</h3> Demographics and baseline characteristics were well balanced between groups. The 90% confidence intervals for the geometric least squares mean ratios of each of the primary PK parameters (AUC<sub>0-inf</sub>, AUC<sub>0-last</sub>, C<sub>max</sub>) were within the predefined equivalence margin of 80% to 125% (Table 1). Secondary PK variables (T<sub>max</sub>, t<sub>1/2</sub>, λ<sub>z</sub>, CL/F, V<sub>z</sub>/F, %AUC<sub>ext</sub>) were also comparable between groups. Mean serum concentrations of tocilizumab observed through 42 days post-dose were comparable between groups (Figure 1). Overall, 55 (38.2%) and 72 (51.4%) subjects reported ≥1 treatment-emergent adverse event (TEAE) in the CT-P47 and EU-tocilizumab groups, respectively. Most of TEAEs were grade 1 or 2 in intensity and TEAEs considered to be related to study drug were reported by 47 (32.6%) and 61 (43.6%) subjects, respectively. Neutrophil count decreased was the most commonly reported TEAE overall (14 [9.7%] and 15 [10.7%] subjects, respectively). There were 3 treatment-emergent serious adverse events (2 [1.4%] and 1 [0.7%] subjects, respectively). Of these, only 1 case was considered to be related to study drug (EU-tocilizumab: headache). Overall, 20 (13.9%) and 29 (20.7%) subjects in the CT-P47 and EU-tocilizumab groups, respectively, had ≥1 post-treatment positive result for anti-drug antibodies (ADA) and 17 (11.8%) and 20 (14.3%) subjects, respectively, had ≥1 positive result post-treatment for neutralizing antibody. Primary PK parameters of AUC<sub>0-inf</sub>, AUC<sub>0-last</sub>, and C<sub>max</sub> were slightly lower in subjects with at least 1 ADA positive compared with those subjects with all ADA negative, at post-dose, among groups in the PK set. <h3>Conclusion</h3> This study demonstrated PK equivalence of CT-P47 to EU-approved tocilizumab in healthy subjects. Safety profiles, including immunogenicity, were comparable between groups. <h3>References</h3> NIL. Abbreviations: EU-tocilizumab, European Union-approved tocilizumab; PK, pharmacokinetic; SD, standard deviation. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Kyung-Sang Yu: None declared, Byungwook Kim: None declared, Dongseong Shin: None declared, Min Kyu Park: None declared, Jun Gi Hwang: None declared, MinGul Kim: None declared, Hyewon Chung: None declared, JongLyul Ghim: None declared, Jae-Yong Chung: None declared, Josef S. Smolen Speakers bureau: AbbVie, AstraZeneca, Astro, BMS, Celltrion, Inc., Chugai, Gilead, Janssen, Lilly, Novartis- Sandoz, Pfizer, R-Pharm, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Astro, BMS, Celltrion, Inc., Chugai, Gilead, Janssen, Lilly, Novartis- Sandoz, Pfizer, R-Pharm, Samsung, Sanofi, Grant/research support from: Abbvie, AstraZeneca and Lilly, Gerd Rüdiger Burmester Consultant of: Celltrion, Inc., Chugai, Sanofi, Roche, Sung Hyun Kim Employee of: Celltrion, Inc., YunJu Bae Employee of: Celltrion, Inc., Dabee Jeon Employee of: Celltrion, Inc., GoEun Yang Employee of: Celltrion, Inc., JaeKyoung Yoo Employee of: Celltrion, Inc., JiHun Bae Employee of: Celltrion, Inc., Edward Keystone Speakers bureau: Amgen, AbbVie, Celltrion., Inc, F.Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Szndoz, Sanofi Genzyme, Consultant of: AbbVie, Amgen, Celltrion., Inc, Myriad Autoimmune, F.Hoffmann-La Roche Inc., Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepis, Grant/research support from: Amgen, Merck, Pfizer Pharmaceuticals.